Mitochondria and Synaptic Plasticity in the Mature and Aging Nervous System

Abstract

Synaptic plasticity in the adult brain is believed to represent the cellular mechanisms of learning and memory. Mitochondria are involved in the regulation of the complex processes of synaptic plasticity. This paper reviews the current knowledge on the regulatory roles of mitochondria in the function and plasticity of synapses and the implications of mitochondrial dysfunctions in synaptic transmission. First, the importance of mitochondrial distribution and motility for maintenance and strengthening of dendritic spines, but also for new spines/synapses formation is presented. Secondly, the major mitochondrial functions as energy supplier and calcium buffer organelles are considered as possible explanation for their essential and regulatory roles in neuronal plasticity processes. Thirdly, the effects of synaptic potentiation on mitochondrial gene expression are discussed. And finally, the relation between age-related alterations in synaptic plasticity and mitochondrial dysfunctions is considered. It appears that memory loss and neurodegeneration during aging are related to mitochondrial (dys)function. Although, it is clear that mitochondria are essential for synaptic plasticity, further studies are indicated to scrutinize the intracellular and molecular processes that regulate the functions of mitochondria in synaptic plasticity.

Fig. (1)

Mitochondrial function in adult synaptic plasticity. Long-term potentiation (LTP) (effects indicated by solid lines) leads to enhanced mitochondrial respiration and thereby ATP production. Cellular ATP concentration influences, on its side, neurotransmitter release. On the other hand, blocking the mitochondrial oxidative phosphorylation (OXPHOS) leads to decrease in ATP levels, drop in neurotransmitter release and significant impairment of LTP. Furthermore, inhibition of the mitochondrial calcium uptake and release machinery results also in impaired synaptic neurotransmission. On the postsynaptic side, mitochondrial calcium uptake as well as mitochondrial gene expression increase following high-frequency stimulation (indicated by and electrode) resulting in enhanced energy production. Therefore, mitochondria play important role in controlling synaptic activity by generating energy in the form of ATP and regulating the intracellular calcium homeostasis.